The objectives of this research proposal are: 1) to elucidate the primary structure of human fibrinogen and its normal variants. 2) to provide information relating to physiologic and pathologic pathways of fibrinogen metabolism. 3) to relate clinical and functional abnormalities of familial fibrinogen disorders to their primary structure. 4) to study the nature and function of non-fibrinogen plasma proteins such as "cold insoluble globulin" (CI-globulin) which interact with fibrinogen. To accomplish these objectives the nature of the primary structure of fibrinogen will be probed by comprehensive analyses of intermediate and advanced plasmic "core" derivatives and non-core fragments. Comparison of plasmic "core" derivatives with circulating catabolites of fibrinogen from normal and pathological samples of blood will be made to elucidate the pathways of fibrinogen catabolism and to examine the possibility that certain of these pathways may be mediated by plasmin or plasmin-like enzymes. Structural analyses of normally occurring fibrinogen variants (such as those of gamma chains) will be further pursued to reveal more exactly the nature of the charge differences between such chains. Similarly, analyses of familial functional abnormalities (e.g. fibrinogen Paris I) will be carried out to identify the molecular basis for the dysfunction. Further characterization of human CI-globulin will be carried out to shed light on its primary structure and on the nature of its function; purification and characterization of rabbit CI-globulin, including preparation of an atibody against it, will be attempted to establish an animal model for the study of CI-globulin turnover and function.